C4591001 COVID-19 BLA Safety and Efficacy Data For - (Data Cutoff 13-Mar-2021) John L. Perez, MD, MBA, MA Vice President, Pfizer Vaccine Clinical ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
C4591001 COVID-19
BLA Safety and
Efficacy Data For
ACIP
(Data Cutoff 13-Mar-2021)
John L. Perez, MD, MBA, MA
Vice President, Pfizer
Vaccine Clinical Research &
Development
30 Aug 2021
Breakthroughs that change patients’ lives Confidential 1
Agenda
1. High level overview of long-term safety analyses for individuals 16+ years of age
2. Adverse events of special interest
3. Efficacy update through 13-March-2021
4. Sequence data on COVID-19 cases through 13-March-2021
5. Pregnancy data through 13-March-2021
Not Covered in presentation but data available for:
HIV+ participants, SARS-CoV-2 +/- at baseline, more than 1 episode COVID-19 cases in placebo
group, placebo participants who developed COVID-19 then received BNT162b2, booster data
Worldwide Research, Development and Medical Confidential 2Phase 2/3 Safety Schema – Started 27 July, 2020
Vaccination period Follow-up period
21 days
apart
Up to
2 years
Active surveillance
for potential COVID-19 symptoms TRIGGERING
telehealth or in-person visit and nasal swab
Reactogenicity in subsets for 16 and above; all 12-15 year olds
7 days 7 days
Non-serious AE: all participants
One month post dose 2
Serious AE: all participants
Six months post dose 2
Deaths: all participants
Through study
Worldwide Research, Development and Medical Confidential 3Original BNT162b2 Participants
Original Placebo Participants Unblinding Date1
Blinded Open-Label
Blinded Placebo-Controlled Follow-Up Period:
Dose 1 1 month after Dose 2
Dose 1 Unblinding date2
Blinded Placebo-Controlled Follow-up Period and
Open-Label Observational Follow-Up Period3:
Dose 1 6 months after Dose 2
Open-Label Observational Follow-Up Period:
Original BNT162b2 Participants
Unblinding Date Data cutoff date
Original Placebo Participants
Unblinding Date Data cutoff date
(Dose 3, Vaccination with BNT162b2)
1 Will vary by participant. Adverse event data analyzed from Dose 1 to unblinding date (on or after
14 December 2020), or from unblinding date to data cutoff date, are reported as incidence rates
adjusted for exposure time.
2 Up to ~5 months after Dose 2.
3 Cumulative BNT162b2 follow-up to at least 6 months after Dose 2, N~3000/age group (16 to 55 years of
age, >55 years of age).
Worldwide Research, Development and Medical Confidential 4Follow-up Time After Dose 2: >16 year olds – Safety Population
BNT162b2 (30 μg) Placebo Total
Total exposure from Dose 2
(N=22026) (N=22021) (N=44047)
to cut-off date
nb(%) n (%) n (%)
Original blinded placebo-controlled follow-up periodDemography for 16-55 and >55 year olds (Safety population)
BNT162b2 Placebo
16-55 Years >55 Years 16-55 Years >55 Years
(N=13069) n (%) (N=8957) n (%) (N=13095) n (%) (N=8926) n (%)
Male 6640 (50.8) 4682 (52.3) 6412 (49.0) 4686 (52.5)
Sex
Female 6429 (49.2) 4275 (47.7) 6683 (51.0) 4240 (47.5)
White 10221 (78.2) 7835 (87.5) 10251 (78.3) 7813 (87.5)
Black or African American 1429 (10.9) 669 (7.5) 1436 (11.0) 682 (7.6)
American Indian or Alaska native 165 (1.3) 56 (0.6) 153 (1.2) 64 (0.7)
Asian 703 (5.4) 249 (2.8) 712 (5.4) 230 (2.6)
Race
Native Hawaiian or other Pacific
43 (0.3) 15 (0.2) 21 (0.2) 11 (0.1)
Islander
Multiracial 437 (3.3) 113 (1.3) 438 (3.3) 95 (1.1)
Not reported 71 (0.5) 20 (0.2) 84 (0.6) 31 (0.3)
Racial desig. Japanese 39 (0.3) 39 (0.4) 41 (0.3) 37 (0.4)
Hispanic/Latino 1657 (18.5) 604 (32.4) 4023 (30.7) 1672 (18.7)
Ethnicity Non-Hispanic/non-Latino 7244 (80.9) 1259 (67.4) 9011 (68.8) 7201 (80.7)
Not reported 56 (0.6) 4 (0.2) 61 (0.5) 53 (0.6)
USA 9251 (70.8) 7541 (84.2) 9267 (70.8) 7527 (84.3)
Country
Others* 3818 (29.2) 1416 (15.8) 3828 (29.2) 1399 (15.7)
Worldwide Research, Development and Medical Confidential 6
*Argentina, Brazil, Germany, South Africa, TurkeySafety
Adverse Events to the Unblinding Date
Blinded Placebo-Controlled Follow-Up
Period:
Dose 1 1 month after Dose 2
Dose 1 Unblinding date
Breakthroughs that change patients’ lives Confidential 7Overall Adverse Events from Dose 1 to Unblinding Date: ≥ 16 years of age
(N=43,847)
Proportion of subjects (%)
100
Reporting at least 1 AE
50
31.7
23.9
16.3
6.0 1.2 1.2 0 0 0.2 0.2 0.1 0.1
0
Any AE Related AE Any SAE Related SAE Withdrawal Death
* due to AE
BNT162b2 Placebo
*Related SAEs: 4 BNT162b2; 1 Placebo
Worldwide Research, Development and Medical Confidential 8Adverse Events ≥1.0% by System Organ Class From Dose 1 to Unblinding
Date: ≥ 16 Years of Age
BNT162b2 (N=21926) Placebo (N=21921)
General disorders and 21.7
1
administration site conditions 4.6
2 8.5
Musculoskeletal and connective tissue disorders
2.8
3 7.3
Nervous system disorders
2.9
3.4
Gastrointestinal disorders4
2.3
1.9
Infections and infestations
2.3
1.3
Injury, poisoning and procedural complications
1.7
1.2
Skin and subcutaneous tissue disorders
0.9
1.0
Respiratory, thoracic and mediastinal disorders
0.9
0 20 40 60 80 100
Percent of Subjects Reporting ≥1% AE
1. Predominantly reflect local reactions at the injection site and systemic reactions of fever and fatigue
2. Predominantly reflects arthralgia and myalgia
3. Predominantly reflects headache
4. Predominantly reflects nausea and diarrhea
Worldwide Research, Development and Medical Confidential 9Higher Frequency PTs Reported in the BNT162b2 7 Days after Dose 1
and 7 Days after Dose 2
These adverse events clustered within the 7 day period after each dose, and are considered to be attributable to
experiencing the reactogenicity events, and plausibly associated with local reactions and systemic events
Dose 1 to 1MPD2 7 days PD1 7 days PD2
BNT169b2 Placebo BNT169b2 Placebo BNT169b2 Placebo
Preferred
(N=21926) (N=21921) (N=21926) (N=21921) (N=21571) (N=21549)
Terms*
n; % (95% CI) n; % (95% CI) n; % (95% CI) n; % (95% CI) n; % (95% CI) n; % (95% CI)
Pain in 185; 0.8 44; 0.2 88; 0.4 12; 0.1 84; 0.4 11; 0.1
extremity (0.7, 1.0) (0.1, 0.3) (0.3, 0.5) (0.0, 0.1) (0.3, 0.5) (0.0, 0.1)
130; 0.6 22; 0.1 48; 0.2 9; 0.0 88; 0.4 10; 0.0
Malaise
(0.5, 0.7) (0.1, 0.2) (0.2, 0.3) (0.0, 0.1) (0.3, 0.5) (0.0, 0.1)
Decreased 39; 0.2 9; 0.0 10; 0.0 6; 0.0 28; 0.1 3; 0.0
appetite (0.1, 0.2) (0.0, 0.1) (0.0, 0.1) (0.0, 0.1) (0.1, 0.2) (0.0, 0.0)
25; 0.1 6; 0.0 10; 0.0 5; 0.0 18; 0.1 1; 0.0
Lethargy
(0.1, 0.2) (0.0, 0.1) (0.0, 0.1) (0.0, 0.1) (0.0, 0.1) (0.0, 0.0)
76; 0.3 25; 0.1 23; 0.1 9; 0.0 51; 0.2 9; 0.0
Asthenia
(0.3, 0.4) (0.1, 0.2) (0.1, 0.2) (0.0, 0.1) (0.2, 0.3) (0.0, 0.1)
17; 0.1 3; 0.0 3; 0.0 0; 0.0 13; 0.1 1; 0.0
Night sweats
(0.0, 0.1) (0.0, 0.0) (0.0, 0.0) (0.0, 0.0) (0.0, 0.1) (0.0, 0.0)
31; 0.1 9; 0.0 11; 0.1 4; 0.0 18; 0.1 4; 0.0
Hyperhidrosis
(0.1,0.2) (0.0, 0.1) (0.0, 0.1) (0.0, 0.0) (0.0, 0.1) (0.0, 0.0)
* Individual participants could report an adverse event more than once
Worldwide Research, Development and Medical Confidential 10Serious Adverse Events with Incidence Rates ≥0.1 by System Organ
Class for ≥ 16 years of age: From Dose 1 to Unblinding Date
BNT162b2 (30 μg)(N=21926) Placebo (N=21921)
System Organ Class n IR/100 PY n IR/100 PY
ANY EVENT 268 3.2 268 3.3
CARDIAC DISORDERS 42 0.5 39 0.5
EYE DISORDERS 5 0.1 3 0
GASTROINTESTINAL DISORDERS 23 0.3 21 0.3
GENERAL DISORDERS & ADMINISTRATION SITE CONDITIONS 10 0.1 4 0
HEPATOBILIARY DISORDERS 12 0.1 7 0.1
INFECTIONS AND INFESTATIONS 50 0.6 57 0.7
INJURY, POISONING, PROCEDURAL COMPLICATIONS 19 0.2 26 0.3
METABOLISM & NUTRITION DISORDERS 4 0 10 0.1
MUSCULOSKELETAL & CONNECTIVE TISSUE DISORDERS 13 0.2 11 0.1
NEOPLASMS BENIGN, MALIGNANT, UNSPECIFIED 39 0.5 35 0.4
NERVOUS SYSTEM DISORDERS 25 0.3 23 0.3
PREGNANCY, PUERPERIUM, PERINATAL CONDITIONS 2 0 6 0.1
PSYCHIATRIC DISORDERS 5 0.1 9 0.1
RENAL & URINARY DISORDERS 11 0.1 8 0.1
REPRODUCTIVE SYSTEM & BREAST DISORDERS 2 0 5 0.1
RESPIRATORY, THORACIC & MEDIASTINAL DISORDERS 14 0.2 14 0.2
VASCULAR DISORDERS
IR/100 PY: incidence rate per 100 person years 12 0.1 13 0.2
Worldwide Research, Development and Medical Confidential 11Related SAEs; ≥ 16 Years of Age From Dose 1 to Unblinding Date
Duration Toxicity
Treatment System Organ Class Preferred Term Dose Rel Day Outcome*
Day Grade
BLOOD AND LYMPHATIC SYSTEM
BNT162b2 Lymphadenopathy (Rt axilla) 1 13 66 2 R
DISORDERS
BNT162b2 CARDIAC DISORDERS Ventricular arrhythmia 2 1 8 3 R
GENERAL DISORDERS AND Shoulder injury related to vaccine
BNT162b2 2 1 153 3 R
ADMINISTRATION SITE CONDITIONS administration
BNT162b2 NERVOUS SYSTEM DISORDERS Paraesthesia (Rt leg) 2 47 Ongoing 2 RG
MUSCULOSKELETAL AND
Placebo Psoriatic arthropathy 2 38 Ongoing 2 N
CONNECTIVE TISSUE DISORDERS
Rel Day = start date of AE relative to the last vaccination;
*R = recovered/resolved; RG = recovering/resolving N = not recovered/not resolved
Worldwide Research, Development and Medical Confidential 12Incidence Rates of Deaths from Dose 1 to Unblinding Date in Subjects ≥ 16
Years of Age: None Related
BNT162b2 (30 μg) Placebo
(N=21926, TE/100 PY=83.4) (N=21921, TE/100 PY=82.2)
Cause of death n IR (/100 PY) n IR (/100 PY)
All Deaths 15 0.2 14 0.2
Acute respiratory failure 0 0 1 0
Aortic rupture 0 0 1 0
Arteriosclerosis 2 0 0 0
Biliary cancer metastatic 0 0 1 0
COVID-19 0 0 2 0
COVID-19 pneumonia 1 0 0 0
Cardiac arrest 4 0 1 0
Cardiac failure congestive 1 0 0 0
Cardio-respiratory arrest 1 0 1 0
Chronic obstructive pulmonary disease 1 0 0 0
Death 0 0 1 0
Dementia 0 0 1 0
Emphysematous cholecystitis 1 0 0 0
Worldwide Research, Development and Medical TE = Total exposure time Confidential 13Incidence Rates of Deaths from Dose 1 to Unblinding date in Subjects ≥ 16
Years of Age: None Related (Cont.)
BNT162b2 (30 μg) Placebo
(N=21926, TE/100 PY=83.4) (N=21921, TE/100PY=82.2)
Cause of death n IR (/100 PY) n IR (/100 PY)
All Deaths 15 0.2 14 0.2
Haemorrhagic stroke 0 0 1 0
Hypertensive heart disease 1 0 0 0
Lung cancer metastatic 1 0 0 0
Metastases to liver 0 0 1 0
Missing 0 0 1 0
Multiple organ dysfunction syndrome 0 0 2 0
Myocardial infarction 0 0 2 0
Overdose 0 0 1 0
Pneumonia 0 0 2 0
Sepsis 1 0 0 0
Septic shock 1 0 0 0
Shigella sepsis 1 0 0 0
Unevaluable event 1 0 0 0
Worldwide Research, Development and Medical TE = Total exposure time Confidential 14Safety
Adverse Events to the Data Cutoff: Dose
1 to 6 Months after Dose 2 in
BNT162b2 Recipients
Blinded Placebo-Controlled Follow-up Blinded Open Label
Period and Open-Label Observational
Follow-Up Period:
Dose 1 6 months after Dose 2
Breakthroughs that change patients’ lives Confidential 15Overall Adverse Events from Dose 1 to 6 Months after Dose 2: ≥ 16 years of
age in Subjects Who Originally Received BNT162b2 (N=12,006)
Proportion of subjects (%)
100
Reporting at least 1 AE
50
28.8
18.7
1.6 0 0 0
0
Any AE Related AE Any SAE Related SAE Withdrawal Death
due to AE
BNT162b2
Worldwide Research, Development and Medical Confidential 16Adverse Events ≥1.0% by System Organ Class from Dose 1 to 6 Months after
Dose 2: ≥ 16 years of age in Subjects Who Originally Received BNT162b2
(N=12,006)
BNT162b2 (N=12,006)
General disorders and
1 16.8
administration site conditions
2
Musculoskeletal and connective tissue disorders 7.5
3
Nervous system disorders 6.0
4
Gastrointestinal disorders 3.4
Infections and infestations 2.5
Injury, poisoning and procedural complications 1.7
Skin and subcutaneous tissue disorders 1.3
Respiratory, thoracic and mediastinal disorders 1.2
0 20 40 60 80 100
Percent of Subjects Reporting ≥1% AE
1. Predominantly reflect local reactions at the injection site and systemic reactions of fever and fatigue
2. Predominantly reflects arthralgia and myalgia
3. Predominantly reflects headache
4. Predominantly reflects nausea and diarrhea
Worldwide Research, Development and Medical Confidential 17Serious Adverse Events ≥0.1% by System Organ Class from Dose 1 to 6
Months after Dose 2: ≥ 16 years of age in Subjects Who Originally Received
BNT162b2
BNT162b2 (30 μg)(N=12,006)
System Organ Class n %
ANY EVENT 190 1.6
CARDIAC DISORDERS 27 0.2
GASTROINTESTINAL DISORDERS 14 0.1
GENERAL DISORDERS & ADMINISTRATION SITE CONDITIONS 7 0.1
HEPATOBILIARY DISORDERS 11 0.1
INFECTIONS AND INFESTATIONS 36 0.3
INJURY, POISONING, PROCEDURAL COMPLICATIONS 16 0.1
MUSCULOSKELETAL & CONNECTIVE TISSUE DISORDERS 9 0.1
NEOPLASMS BENIGN, MALIGNANT, UNSPECIFIED 25 0.2
NERVOUS SYSTEM DISORDERS 23 0.2
RENAL & URINARY DISORDERS 9 0.1
RESPIRATORY, THORACIC & MEDIASTINAL DISORDERS 10 0.1
Worldwide Research, Development and Medical Confidential 18Adverse Events of
Special Interest
and other important terms
evaluated during the
placebo-controlled portion
of the clinical trial
Breakthroughs that change patients’ lives Confidential 19FDA Requested AEs of Clinical Interest
• Hypersensitivity/Anaphylaxis
• Blinded Control period:
• 3 SAEs of allergic reaction (previously reported) and not related:
• Anaphylactic reaction after bee sting (BNT162b2 8 days post dose 2)
• Drug hypersensitivity to antibiotic (BNT162b2 9 days post dose 2)
• Anaphylactic shock due to ant bite (Placebo 18 days post dose 2)
• Open Label follow-up period:
• 1 subject reported anaphylactoid reaction – assessed to be related:
• Female 17 years old; medical history of multiple allergies; 2 days post dose 3 of BNT162b2
experienced hives; self-administered epinephrine; and resolved 10-30 mins later;
• Not medically attended
• Importantly, the participant received a second dose of BNT162b2 outside the study 40 days after the
first and no allergic reaction was reported.
Worldwide Research, Development and Medical Confidential 20FDA Requested AEs of Clinical Interest: Bell’s Palsy
• First 6 cases were reported in the initial EUA
Days from Duration
Case Treatment Period Sex Age Related
last dose (Days)
1* BNT162b2 placebo-controlled Male 53 3 3 Y
2 BNT162b2 placebo-controlled Male 40 9 68 Y
3** BNT162b2 placebo-controlled Male 62 48 30 N
4 BNT162b2 placebo-controlled Male 70 37 21 N
1 Placebo placebo-controlled Female 71 32 15 N
2 Placebo placebo-controlled Male 73 102 - N
5*** BNT162b2 Crossover Female 19 9 - Y
6 BNT162b2 Crossover Female 22 2 - Y
7 BNT162b2 Crossover Female 34 4 11 Y
8 BNT162b2 Unblinded followup Male 51 154 - N
* Diabetes ** Bell’s palsy; TIA *** 3 prior episodes of Bell’s palsy
Worldwide Research, Development and Medical Confidential 21FDA Requested AEs of Clinical Interest (cont.)
• Lymphadenopathy
• 83 / 21926 (0.4%) in BNT162b2 group
• 7 / 21921 (0.03%) in placebo group
• primarily mild to moderate with 3 severe events in BNT162b2 group
• Median onset between dose 1 and dose 2: 5.5 days for BNT162b2
• Median onset after dose 2: 2.0 days for BNT162b2
• Median duration: 5.5 days for BNT162b2
• Appendicitis: None were considered related to study intervention by the
investigator
• Blinded control period
• BNT162b2 group: 15 / 21926 (0.07%)
• Placebo group: 12 / 21921 (0.06%)
Worldwide Research, Development and Medical Confidential 22CDC AESIs
• Only those events where there was an imbalance were investigated in ~46,000 subjects
• Angioedema* 30 (0.14%) vs 29 (0.13%)
• Hypersensitivity*
• Mostly skin and subcutaneous tissue disorders: BNT162b2 134 (0.61%); Placebo 119 (0.54%)
• rash BNT162b2 62 (0.28%); Placebo 52 (0.24%)
• rash maculo-papular BNT162b2 7 (0.03%); Placebo 4 (0.02%)
• rash papular BNT162b2 1 (0.00%); Placebo 0 (0.0%)
*Standard MedDRA Query
Worldwide Research, Development and Medical Confidential 23CDC AESIs (cont.)
• Demyelination SMQ
• Optic neuritis: 2 in the BNT162b2; 0 in placebo
• 41 year old male, received 2 doses BNT162b2, then quadrivalent influenza vaccine 17 days after dose 2.
• 80 days after last BNT162b2 dose, developed optic neuritis and visual loss in left eye
• Investigations were negative; treated with IV methylprednisolone and resolved after 14 days of treatment
• Not related to vaccine by investigator
• 30 year old female, received 2 doses of BNT162b2 and had significant medical history of migraines, hypothyroidism
and familial hypercholesterolemia
• 103 days after last BNT162b2 dose, developed severe optic neuritis in right eye with pain, photophobia, and decreased visual
acuity and alterations of colour perception
• MRI showed right optic nerve enhancement; treated with IV methylprednisolone resulted in improvement, but could not be tapered
without symptoms recurring
• Not related by investigator, and ongoing at time of data cutoff.
• Guillain-Barre Syndrome
• One SAE in the Placebo group
Worldwide Research, Development and Medical Confidential 24CDC AESIs (cont.): The following terms were not reported in the study
Acute disseminated encephalomyelitis Narcolepsy
Transverse myelitis Cataplexy
Multiple sclerosis Immune thrombocytopaenia
Chronic inflammatory demyelinating polyneuropathy Thrombotic thrombocytopenic purpura
Encephalitis Disseminated intravascular coagulation
Myelitis Kawasaki disease
Encephalomyelitis Multisystem inflammatory syndrome in children
Meningoencephalitis Multisystem inflammatory syndrome in adults
Ataxia Acute respiratory distress syndrome
• 2 cases of bacterial meningitis were reported in the study
Worldwide Research, Development and Medical Confidential 25Other AESIs of Interest
Additional terms beyond those designated by the CDC as AESIs were evaluated to assess potential
imbalances between the BNT162b2 and placebo groups during the blinded placebo-controlled
follow-up period.
• Acute Myocardial Infarction
• Acute myocardial infarctions (includes PTs of acute myocardial infarction, acute coronary syndrome,
coronary artery occlusion, and myocardial infarction).
o BNT162b2 (total of 11 events)
o Placebo (total of 17 events)
• Most of these events had onset distant to (ie, >30 days following) receipt of vaccine or placebo. None of
these events were assessed by the investigator as related to study intervention. Outcome was fatal in 2
participants in the placebo group and resolved or resolving in the other cases.
Worldwide Research, Development and Medical Confidential 26Other AESIs of Interest (cont.)
• Encephalopathy
• 2 events reported in the BNT162b2 group, none in Placebo
• One was a SAE of toxic encephalopathy 64 days after Dose 2 which resolved 8 days later.
• One was a SAE of uraemic encephalopathy 36 days after Dose 2 which resolved 3 days later.
• Both events were assessed by the investigator as not related to study intervention.
• Multisystem Inflammatory Syndrome
• One SAE in the Placebo group of multiple organ dysfunction syndrome secondary to
COVID-19.
• Myocarditis
• Once case in the Placebo group
Worldwide Research, Development and Medical Confidential 27Other AESIs of Interest (cont.)
• Pericarditis
• 1 event reported in the BNT162b2 older age group (66 year old white male)
• Onset was 29 days after Dose 2 and was ongoing at the time of the data cut-off
• Not related to study intervention
• Pulmonary Embolism (includes PTs of Pulmonary embolism; Pulmonary thrombosis; Pulmonary
venous thrombosis; Pulmonary artery thrombosis)
• 8 cases in the BNT162b2 group and 8 cases in Placebo
• Stroke, Haemorrhagic (includes PTs of Haemorrhagic stroke; Cerebral haemorrhage;
Haemorrhagic cerebral infarction; Basal ganglia haemorrhage; Brain stem haemorrhage;
Cerebellar haemorrhage; Subarachnoid haemorrhage; Intraventricular haemorrhage
• 4 cases in BNT162b2 and 3 cases in placebo group
• Stroke, Ischaemic
• 8 cases in BNT162b2 group and 8 cases in Placebo: 8
Worldwide Research, Development and Medical Confidential 28Other AESIs of Interest (cont.)
• Thrombocytopenia: BNT162b2 2 vs Placebo 2
• Platelet count decrease: 1 in BNT162b2 group; 0 in Placebo group
• Thrombocytopenia: 1 in BNT162b2 group; 2 in Placebo group
• BNT162b2
• Late 60s y/o male, med hx alcoholic cirrhosis, esophageal varices & ulcers. On Day 19 following dose 1 participant was hospitalized for
3 days with GI bleed due to esophageal ulcers. Bloodwork revealed a haematocrit 22.9 and platelet count of 70. The AE of
thrombocytopenia was assessed by investigator as due to cirrhosis (not related to study intervention); ongoing.
• Mid 80 y/o male, hospitalized with COPD exacerbation, pneumonia (COVID-19 negative) and sepsis on Day 120 post dose 2. Initial labs:
haemoglobin 12 g/dL, platelets 21.4 K/uL; repeat labs next day: haemoglobin 10.5 g/dL, platelets 177 K/uL The AE of low platelet count
was assessed by investigator as not related to study intervention; resolved.
• Venous Thromboembolism
• 9 cases in BNT162b2 and 9 cases in Placebo
None of these venous events were associated with thrombocytopenia.
Worldwide Research, Development and Medical Confidential 29Pregnancy
Disposition of Participants 16 Years of age and Older, Phase 2/3, Safety Populations who Experienced
Pregnancy through 13 March 2021
BNT162b2a Placebob Total
(N=22026) (N=22021) (N=44047)
n (%) n (%) n (%)
Total number of pregnancies 42 (0.2) 47 (0.2) 89 (0.2)
Withdrawal from vaccination due 5 (0.0) 5 (0.0) 10 (0.0)
to pregnancy
Timing of pregnancy
Completed 1 dose 5 (0.0) 8 (0.0) 13 (0.0)
Completed 2 doses 37 (0.2) 39 (0.2) 76 (0.2)
Timing of last dose relative to
pregnancy
Within 30 days of pregnancy 13 (0.1) 21 (0.1) 34 (0.1)
>30 days after pregnancy 29 (0.1) 26 (0.1) 55 (0.1)
Spontaneous Abortions 3 (0.0) 7 (0.0) 10 (0.0)
Miscarriages 3 (0.0) 5 (0.0) 8 (0.0)
Elective Abortions 0 1 (0.0) 1 (0.0)
Fetal demise 0 0 0
Major birth defects 0 0 0
Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary
a. Includes data from Dose 1 through 13 March 2021 for participants who originally received BNT162b2.
b. Includes data from Dose 1 to before the first dose of BNT162b2 or through 13 March 2021 for participants who originally received placebo.
Worldwide Research, Development and Medical Confidential 30Efficacy data
March 13, 2021 Data Cutoff
Breakthroughs that change patients’ lives Confidential 31First COVID-19 Occurrence From 7 Days After Dose 2
Subjects ≥16 Years of Age – Evaluable Efficacy Population – March 13, 2021 Cutoff
Subjects WITHOUT Evidence of Infection Prior to 7 days after Dose 2
BNT162b2 (30 µg) Placebo
N=19,993 N=20,118
Surveillance Surveillance VE
Efficacy Endpoint n Time (n) n Time (n) (%) (95% CI)
First COVID-19 occurrence
77 6.092 (19711) 833 5.857 (19741) 91.1 (88.8, 93.1)
≥7 days after Dose 2
Total surveillance time: 1000 person-years for all subjects within each group at risk for the endpoint.
Worldwide Research, Development and Medical Confidential 32First COVID-19 Occurrence From 7 Days After Dose 2
Subjects ≥16 Years of Age – Evaluable Efficacy Population
Subjects WITH or WITHOUT Evidence of Infection Prior to 7 days after Dose 2
BNT162b2 (30 µg) Placebo
N=21,047 N=21,210
Surveillance Surveillance VE
Efficacy Endpoint n Time (n) n Time (n) (%) (95% CI)
First COVID-19 occurrence
81 6.340 (20533) 854 6.110 (20595) 90.9 (88.5, 92.8)
≥7 days after Dose 2
Total surveillance time: 1000 person-years for all subjects within each group at risk for the endpoint.
Worldwide Research, Development and Medical Confidential 33First COVID-19 Occurrence From 7 Days After Dose 2
Subjects ≥16 Years of Age – Evaluable Efficacy Population: Subgroups
Subjects WITH or WITHOUT Evidence of Infection Prior to 7 days after Dose 2
BNT162b2 Placebo
N=21,047 N=21,210
n n VE (%) (95% CI)
Overall 81 854 90.9 (88.5, 92.8)
16-17 years 0 11 100.0 (62.4, 100.0)
18-64 years 74 715 90.0 (87.3, 92.3)
Age
65-74 years 6 102 94.3 (87.1, 98.0)
≥75 years 1 26 96.2 (77.2, 99.9)
Male 44 399 89.6 (85.8, 92.6)
Sex
Female 37 455 92.0 (88.8, 94.4)
White 69 749 91.1 (88.6, 93.2)
Black or African American 4 49 92.0 (78.1, 97.9)
Race Asian 3 24 88.0 (60.6, 97.7)
Multiracial 5 22 80.1 (46.1, 94.1)
Not reported 0 6 100.0 (1.4, 100.0)
Hispanic/Latino 32 240 87.1 (81.3, 91.4)
Ethnicity
Non-Hispanic/Non-Latino 48 614 92.5 (89.9, 94.5)
Argentina 16 110 85.7 (75.7, 92.1)
Brazil 14 82 84.2 (71.9, 91.7)
Germany 0 1 100.0 (-3868.6, 100.0)
Country
South Africa 0 10 100.0 (56.6, 100.0)
Turkey 0 6 100.0 (22.2, 100.0)
Worldwide Research, Development and Medical Confidential 34
USA 51 645 92.4 (89.9, 94.4)First COVID-19 Occurrence From 7 Days After Dose 2
Subjects ≥16 Years of Age – Evaluable Efficacy Population: Risk Factor Subgroups
Subjects WITH or WITHOUT Evidence of Infection Prior to 7 days after Dose 2
BNT162b2 Placebo
N=22,166 N=22,320
n n VE (%) (95% CI)
Overall 81 854 90.9 (88.5, 92.8)
Yes 36 402 91.4 (87.9, 94.1)
At risk1
No 45 452 90.4 (86.9, 93.1)
16-64 and not at risk 44 397 89.3 (85.4, 92.4)
Age group 16-64 and at risk 30 329 91.2 (87.3, 94.2)
at risk ≥65 and not at risk 1 55 98.2 (89.6, 100.0)
≥65 and at risk 6 73 92.1 (82.0, 97.2)
Yes 28 314 91.3 (87.1, 94.3)
Obese2
No 53 540 90.6 (87.5, 93.1)
16-64 and not obese 49 458 89.8 (86.2, 92.5)
Age group 16-64 and obese 25 268 90.9 (86.3, 94.2)
and obese ≥65 and not at obese 4 82 95.3 (87.6, 98.8)
≥65 and obese 3 46 93.4 (79.5, 98.7)
1 At least one of Charlson Comorbidity index or obesity
Worldwide Research, Development and Medical Confidential 35
2 Obesity: BMI ≥ 30 kg/m2First COVID-19 Occurrence After Dose 1
BNT162b2 (30 μg) Placebo
N=23,040 N=23,037
n n VE (%) (95% CI)
COVID-19 occurrence after Dose 1 131 1034 87.8 (85.3, 89.9)
After Dose 1 and before Dose 2 46 110 58.2 (40.5, 71.0)
After Dose 1 toFirst Severe COVID-19 Occurrence From 7 Days After Dose 2
Subjects ≥16 Years of Age – Evaluable Efficacy Population
Subjects WITHOUT Evidence of Infection Prior to 7 days after Dose 2
BNT162b2 (30 µg) Placebo
N=19,993 N=20,118
Surveillance Surveillance
Efficacy Endpoint n Time (n) n Time (n) VE (%) (95% CI)
First Severe COVID-19
occurrence ≥7 days 1 6.103 (19711) 21 5.971(19741) 95.3 (71.0, 99.9)
after Dose 2
Total surveillance time: 1000 person-years for all subjects within each group at risk for the endpoint.
Worldwide Research, Development and Medical Confidential 37No apparent SARS-CoV-2 lineage pattern among vaccine breakthrough cases that
would suggest meaningfully reduced BNT162b2 efficacy against any variant
through 13-March-2021
Summary of SARS-CoV-2 Variants of Concern or Variants of Interest for the First COVID-19 Occurrence
From 7 Days After Dose 2 – Blinded Placebo-Controlled Follow-up Period – Subjects 12 years & older
With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo Total
(Na=81) (Na=873) (Na=954)
SARS-CoV-2 Lineageb nc (%) nc (%) nc (%)
(Location of lineage first identified)
B.1.1.7 (United Kingdom) 0 3 (0.3) 3 (0.3)
B.1.351 (South Africa) 0 9 (1.0) 9 (0.9)
B.1.427/B.1.429 (USA) 1 (1.2) 23 (2.6) 24 (2.5)
B.1.525 (UK and Nigeria) 0 1 (0.1) 1 (0.1)
B.1.526 (USA) 0 1 (0.1) 1 (0.1)
B.1.616 (France) 0 0 0
B.1.617 (India) 0 0 0
B.1.618 (India) 0 0 0
P.1 (Brazil/Japan) 1 (1.2) 1 (0.1) 2 (0.2)
P.2 (Brazil) 6 (7.4) 40 (4.6) 46 (4.8)
P.3 (Philippines) 0 0 0
Other 66 (81.5) 755 (86.5) 821 (86.1)
Unknownd 7 (8.6) 33 (3.8) 40 (4.2)
Not sequenced 0 8 (0.9) 8 (0.8)
Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects with first COVID-19 occurrence. This value is the denominator for the percentage calculations.
b. Based on PANGO lineages (cov-lineages.org).
Worldwide Research, Development and Medical c. n = Number of subjects with the specified characteristic. Confidential 38
d. Include indeterminate result and not quantifiable (QNS) samples.Overall Conclusions
• In Phase 2/3, updated efficacy analysis continued to show that BNT162b2 at 30 µg provided a
high level of protection against COVID-19. This was shown in participants across various
demographic subgroups. Severe cases were observed predominantly in the placebo group.
• The tolerability and safety profile of BNT162b2 30 µg in participants ≥16 years of age at up to 6
months after Dose 2 was acceptable throughout the follow-up period (to the data cutoff date) and
consistent with results previously reported.
Worldwide Research, Development and Medical Confidential 39You can also read
